The Mechanism Of Tacrolimus On Klotho Protein In Rats With Adriamycin Nephropathy

Objective:To investigate the effect of tacrolimus on klotho protein of adriamycin nephrosis rats and to discuss the possible mechanism.Methods:Sixty male wistar rats were randomly divided into adriamycin nephropathy rats?ADR?and normal control group?NC?,.ADR was induced by a single tail vein injection of doxorubicin?5 mg/kg?.The normal control group was injected with normal saline.ADR treated with normal saline?ADR group?,ADR treated with olmesartan medoxomil(10mg.kg^-1.d^-1)?OLM group?and ADR treated with tacrolimus(0.5mg.kg^-1.d^-1)?FK506 group?.After 4 weeks,8 weeks and 12weeks,the urine protein excretion were measured.SOD and MDA levels in renal cortex were also measured.Observation of renal histomorphology by HE stain.The expression of klotho in adriamycin nephropathy rat kidney tissue was detected by Real-time PCR and Western blotting.Results:?1?In the same period,24-h urine protein excretion were significantly increased in ADR than in NC group,Compared with ADR group,the 24-h urine protein excretion in OLM group and FK506 group was lower,24-h urine protein excretion were significantly decreased in FK506 group than in OLM group?F=126.969⁷81.905,P<0.05?.In the ADR,with the progress of time,24-h urine protein excretion were significantly increased in ADR group,while24-h urine protein excretion were significantly decreased in OLM group and FK506 group?F=16.957¹82.942,P<0.05?.?2?In the same period,SOD activities in renal tissues were significantly decreased in ADR than in NC group,Compared with ADR group,SOD activities in OLM group and FK506 group was higher,SOD activities were significantly increased in FK506 group than in OLM group?F=125.782⁴67.589,P<0.05?.In the ADR,with the progress of time,SOD activities in renal cortex were significantly decreased in ADR group,while SOD activities were significantly increased in OLM group and FK506group?F=6.871⁵7.072,P<0.05?.In the same period,MDA levels in renal tissues were significantly increased in ADR than in NC group,Compared with ADR group,MDA levels in OLM group and FK506 group was lower,MDA levels were significantly decreased in FK506 group than in OLM group?F=52.782¹62.589,P<0.05?.In the ADR,with the progress of time,MDA levels in renal cortex were significantly increased in ADR group,while MDA levels were significantly decreased in OLM group and FK506 group?F=6.871⁵7.072,P<0.05?.?3?In the same period,klotho levels were significantly decreased in ADR than in NC group,Compared with ADR group,klotho levels in OLM group and FK506 group was higher,klotho levels were significantly increased in FK506 group than in OLM group?F=116.671⁶09.513,P<0.05?.In the ADR,with the progress of time,klotho levels were significantly decreased in ADR group,while klotho levels were significantly increased in OLM group and FK506 group?F=10.985⁴0.485,P<0.05?.Conclusions:klotho decrease in rats with adriamycin nephropathy.The tacrolimus can significantly increase the expression of klotho protein and reduce oxidative stress than olmesartan medoxomil in rats with adriamycin nephropathy.